The present invention generally relates to a method for therapeutically treating the inner ear. More particularly, the invention involves a specialized, minimally-invasive technique for transporting therapeutic agents (e.g. drugs and other pharmaceutical compositions) into the inner ear from the middle ear in a highly effective manner.
In order to treat ear disorders, it may often be necessary to deliver therapeutic agents to various ear tissues in a controlled, safe, and efficient manner. For example, a variety of structures have been developed which are capable of delivering/administering therapeutic agents into the external auditory canal of the outer ear. U.S. Pat. No. 4,034,759 to Haerr discloses a hollow, cylindrical tube manufactured of sponge material (e.g. dehydrated cellulose) which is inserted into the external auditory canal of a patient. When liquid medicines are placed in contact with the tube, it correspondingly expands against the walls of the auditory canal. As a result, accidental removal of the tube is prevented. Furthermore, medicine materials absorbed by the tube are maintained in contact with the walls of the external auditory canal for treatment purposes. Other absorbent devices designed for treatment of the external auditory canal and related tissue structures are disclosed in U.S. Pat. No. 3,528,419 to Joechle, U.S. Pat. No. 4,159,719 to Haerr, and U.S. Pat. No. 2,642,065 to Negri. The Negri patent specifically describes a medicine delivery device with an internally-mounted, frangible medicine container which, when broken, releases liquid medicines into an absorbent member.
However, the delivery of therapeutic agents in a controlled and effective manner is considerably more difficult with respect to tissue structures of the inner ear (e.g. those portions of the ear surrounded by the otic capsule bone and contained within the temporal bone which is the most dense bone tissue in the entire human body). The same situation exists in connection with tissue materials which lead into the inner ear (e.g. the round window membrane). Exemplary inner ear tissue structures of primary importance for treatment purposes include but are not limited to the cochlea, the endolymphatic sac/duct, the vestibular labyrinth, and all of the compartments (and connecting tubes) which include these components. Access to these and other inner ear tissue regions is typically achieved through a variety of structures, including but not limited to the round window membrane, the oval window/stapes footplate, the annular ligament, and the otic capsule/temporal bone, all of which shall be considered “middle-inner ear interface tissue structures” as described in greater detail below. Furthermore, as indicated herein, the middle ear shall be defined as the physiological air-containing tissue zone behind the tympanic membrane (e.g. the ear drum) and ahead of the inner ear.
The inner ear tissues listed above are of minimal size and only readily accessible through invasive microsurgical procedures. In order to treat various diseases and conditions associated with inner ear tissues, the delivery of medicines to such structures is often of primary importance. Representative medicines which are typically used to treat inner ear tissues include but are not limited to urea, mannitol, sorbitol, glycerol, lidocaine, xylocaine, epinephrine, immunoglobulins, sodium chloride, steroids, heparin, hyaluronidase, aminoglycoside antibiotics (streptomycin/gentamycin), antioxidants, neurotrophins, nerve growth factors, various therapeutic peptides, and polysaccharides. Of particular interest in this list are compounds which are used to alter the permeability of the round window membrane within the ear using, for example, hyaluronidase and iontophoretic techniques (defined below). Likewise, the treatment of inner ear tissues and/or fluid cavities may involve altering the pressure, volume, electrical activity, and temperature characteristics thereof. Specifically, a precise balance must be maintained with respect to the pressure of various fluids within the inner ear and its associated compartments. Imbalances in the pressure and volume levels of such fluids can cause various problems, including but not limited to conditions known as endolymphatic hydrops, endolymphatic hypertension, perilymphatic hypertension, perilymphatic hydrops, perilymphatic fistula, intracochlear fistula, Meniere's disease, tinnitus, vertigo, hearing loss related to hair cell or ganglion cell damage/malfunction, and ruptures in various membrane structures within the ear.
Of further interest regarding the delivery of therapeutic agents to the middle ear, inner ear, and middle-inner ear interface tissue structures are a series of related and co-owned patents, namely, U.S. Pat. Nos. 5,421,818; 5,474,529, and 5,476,446 all to Arenberg et al. which are likewise all incorporated herein by reference. Each of these patents discloses a medical treatment apparatus designed to deliver fluid materials to internal ear structures. U.S. Pat. No. 5,421,818 describes a treatment system which includes a tubular stem attached to a reservoir portion with an internal cavity designed to retain a supply of therapeutic fluid compositions therein. The side wall of the reservoir portion further comprises fluid transfer means (e.g. pores, a semi-permeable membrane, and the like). Contact between the fluid transfer means and the round window membrane in a patient allows fluid materials to be delivered on-demand to the round window membrane, followed by diffusion of the fluid materials through the membrane into the inner ear. U.S. Pat. No. 5,474,529 involves a therapeutic treatment apparatus with a plurality of reservoir portions (e.g. a first and a second reservoir portion in a preferred embodiment) which are connected to multiple tubular stems that are designed for implantation into, for example, the endolymphatic sac and duct using standard microsurgical techniques. Finally, U.S. Pat. No. 5,476,446 discloses a therapeutic treatment apparatus which includes a reservoir portion for retaining liquid medicine materials therein, a first tubular stem on one side of the reservoir portion, and a second tubular stem on the opposite side of the reservoir portion. The second stem is designed to reside within the external auditory canal of a patient lateral to the ear drum, while the first stem is sized for placement within an opening formed in the stapes footplate/annular ligament so that medicine materials in fluid form can be delivered into the inner ear from the reservoir portion (which resides in the middle ear cavity medial to the ear drum).
A different approach for transferring materials into and out of the inner ear via the round window niche/round window membrane is disclosed in co-owned pending U.S. patent application Ser. No. 08/874,208 (Arenberg et al.) entitled “INNER EAR FLUID TRANSFER AND DIAGNOSTIC SYSTEM” and filed on Jun. 13, 1997 which is incorporated herein by reference. This application describes a system in which one or more fluid transfer conduits are provided which are operatively connected to a “cover member” that is designed for placement on top of the niche (e.g. at its point of entry) or within the niche. The cover member is used to create a “fluid-receiving zone” (or “inner ear fluid transfer space”) which is partially or entirely sealed in order to facilitate fluid transfer into and out of the inner ear. In one embodiment, the cover member consists of a thin, solid, plate-like structure that is secured in position on top of the niche at its point of entry as previously noted. Alternatively, the cover member may comprise a portion of flexible and compressible material which, during placement within the round window niche, is compressed and thereafter allowed to expand once the portion of compressible material is positioned within the niche. As a result, the cover member can engage the internal side wall of the round window niche, thereby creating the fluid-receiving zone (“inner ear fluid transfer space”) between the compressible cover member and the round window membrane. Representative compositions used to construct the portion of compressible material associated with the cover member in this particular embodiment optimally involve foam-type products including but not limited to polyethylene foam, polyether foam, polyester foam, polyvinyl chloride foam, polyurethane foam, and sponge rubber (e.g. synthetic or natural), all of which are of the closed cell variety. Such materials are non-fluid-absorbent in accordance with the substantial lack of open cells therein. Specifically, the non-fluid-absorbent character of these materials results from the closed cell structure thereof which prevents fluid materials from being absorbed compared with open cell (absorbent) foam products.
A still further system for transferring materials into and out of the inner ear via the round window niche/round window membrane is disclosed in co-owned pending U.S. patent application Ser. No. 09/121,460 (Arenberg et al.) entitled “FLUID TRANSFER AND DIAGNOSTIC SYSTEM FOR TREATING THE INNER EAR” and filed on Jul. 23, 1998 which is also incorporated herein by reference. This particular system employs a fluid transfer conduit which includes one or more passageways therethrough. The fluid transfer conduit may also have a semipermeable membrane associated therewith to control fluid flow. Attached to the conduit is an inflatable bladder sized for insertion within the round window niche. When inflated, the bladder engages the internal side wall of the niche, thereby securing the bladder and part of the conduit within the niche. The conduit can then transfer fluids to and from the niche and the fluid-permeable round window membrane therein. Bladder inflation may be achieved through one of the passageways within the conduit which can deliver an inflation fluid into the bladder. Also, the conduit may include an elongate conductive diagnostic member for transferring electrical potentials to and from the inner ear (via the round window membrane).
Notwithstanding the approaches described above which provide a number of benefits, the present invention involves an improved minimally-invasive drug delivery system and method which offers many additional advantages including: (1) the repeatable and sustained active/passive delivery of therapeutic agents into the inner ear through the round window membrane (or other middle-inner ear interface structures as discussed further below); (2) the delivery of a wide variety of therapeutic agents (e.g. pharmaceutical preparations) in a safe and direct manner through the use of controlled-release carrier materials; (3) the accomplishment of effective drug delivery without overly invasive surgical procedures; (4) the ability to initiate a single drug delivery step which will result in the controlled/sustained delivery of therapeutic agents into the inner ear of a patient without further medical procedures, monitoring, and patient discomfort; and (5) achievement of the benefits described above through the use of a controlled release carrier media material which is combined with one or more therapeutic agents (e.g. pharmaceutical compositions) and placed into the round window niche of a patient in the form of a mass consisting of a pellet or other structural unit. In addition, as outlined further below, the carrier medial material and therapeutic agent(s) can be placed into the round window niche in the form of a gel/paste that is initially injected into the niche to form the mass in situ. The mass of material associated with the carrier media composition (which is positioned adjacent to or directly against the round window membrane) subsequently releases the therapeutic agents over time. As a result, the therapeutic agents travel through the round window niche, followed by movement into and through the round window membrane. The therapeutic agents thereafter enter the inner ear for treatment purposes. This passive, minimally-invasive drug delivery system allows pharmaceutical compositions to be effectively delivered into the inner ear of a patient in a controlled and efficient fashion. In this manner, a highly accurate transfer system for therapeutic agents is created. Accordingly, the present invention represents an advance in the art of inner ear treatment, diagnosis, and medicine delivery as described in detail below.